KR940008696A - 프로드럭 활성화를 위한 융합 단백질 - Google Patents

프로드럭 활성화를 위한 융합 단백질 Download PDF

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KR940008696A
KR940008696A KR1019930020298A KR930020298A KR940008696A KR 940008696 A KR940008696 A KR 940008696A KR 1019930020298 A KR1019930020298 A KR 1019930020298A KR 930020298 A KR930020298 A KR 930020298A KR 940008696 A KR940008696 A KR 940008696A
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게르만 마티아스
지이만 게르하르트
보슬레트 클라우스
체흐 외르크
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스타인, 부크
베링베르케 아크티엔게젤샤프트
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Abstract

본 발명은 세포독성이 적거나 없는 화합물(프로드럭)을 세포독성 화합물 (약물)로 대사할 수 있는 효소 하나이상의 결합하는, 단일 폴리펩타이드 쇄로 구성된 항원 결합 영역을 포함하는 화합물에 관한 것이다. 공유 결합된 탄수화물이 폴리펩타이드 쇄상에 존재하는 것이 유리하다.

Description

프로드럭 활성화를 위한 융합 단백질
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 안티-유전자형 친화 크로마토그래피로 정제한 sFv-huβ-Gluc 융합단백질을 다시 TSK 겔 G 3000 SW XL컬럼 상에서 크로마토그래피한 결과를 나타낸다.
제2도에는 단쇄 Fv(sFv)를 올리고 2577및 2561로 증폭시키고 Xba I /Hind Ⅲ로 분해된 벡터 pUC 19내에 클론시키는 과정을 나타낸다.
제3도는 사람 β-글루쿠로니다제 유전자를 올리고 2562 및 2540으로 증폭시키고 Bg1 Ⅱ/Hind Ⅲ로 절단된 플라스미드 sFv 431/26내에 결합시키는 공정을 나타낸다.

Claims (26)

  1. 프로드럭-활성화 효소하나 이상에 결합되는, 단일 폴리펩타이드 쇄로 구성된 항원 결합 영역을 포함하는 화합물.
  2. 제1항에 있어서, 화합물이 공유 결합된 탄수화물을 갖는 화합물.
  3. 제1항 또는 제2항에 있어서, 항체 결합 영역이 항체 중쇄의 가변 도메인 및 항체 경쇄의 가변 도메인(sFv단편)을 포함하는 화합물.
  4. 제1항 또는 제2항에 있어서, 항체 결합 영역이 종양-관련된 항원(TAA)에 결합하는 화합물.
  5. 제3항에 있어서, TAA가 N-CAM, PEM, EGF-R, 시알릴-레a(Sialyl-LEa), 시알릴-레x(Sialyl-Lex), TFβ, GICA, GD3, GD2, TAG72, GA125, MAb L6 으로 정의된 24내지 25KDa당단백질, 또는 CEA, 바람직하게는 CEA인 화합물.
  6. 제1항 내지 제5항중 어느 한 항에 있어서, 효소가 락타마제, 바람직하게 바실루스 세레우스(Bacillus cereus) Ⅱβ-락타마제, 피로글루타메이트 아미노펩티다제, D-아미노펩티다제, 옥시다제, 퍼옥시다제, 포스파타제, 하이드록시니트릴리아제, 프로테아제, 에스테라제, 카복시펩티다제, 바람직하게는 슈도모나즈로부터의 카복시펩티다제 G2 또는 글리코시다제인 화합물.
  7. 제6항에 있어서, 효소가 β-글루쿠로니다제, 바람직 하게는 이. 콜라이 고바야시아 니포니카, 세칼 세리얼 또는 사람 β-글루쿠로니다제인 화합물.
  8. 제1항 내지 제7항중 어느 한 항에 있어서, 항원 결합 영역이 펩타이드 링커를 통해 효소가 연결되는 화합물.
  9. 제1항 내지 제8항중 어느 한 항에 있어서, 당화가 화학방법에 의해서 또는 적합한 발현시스템 선별에 의해 발생하는 화합물.
  10. 제1항 내지 제9항중 어느 한 항에 있어서, 사카로마이세스 세레비지애 또는 보다 유리하게는 한세눌라 폴리모파에서 분비 발현을 수행하는 화합물.
  11. 제1항 내지 제9항중 어느 한 항에 있어서, 이.콜라이에서 발현된 후 화학적으로 당화, 바람직하게는 갈락토실화되고/되거나 만노실화되는 화합물.
  12. 제1항 내지 제9항중 어느 한 항에 있어서, 이.콜라이에서 페리플라스믹 발현을 수행한 sFv-β-락타마제 융합 단백질이 화학적으로 당화, 바람직하게는 갈락토실화 되고/되거나 만노실화 되는 화합물.
  13. 제1항 내지 제9항중 어느 한 항에 있어서, sFv-β-락타마제 융합 단백질이 사카로마이세스 세레비지애 또는 힌세눌라 폴리모파에서 분비 발현을 수행하는 화합물.
  14. 제1항 내지 제8항중 어느 한 항에 따른 화합물을 암호화하는 핵산
  15. 제14항에 있어서, CEA에 대해 사람화된 sFv단편 및 사람 β-글루쿠로니다제를 암호화하는 핵산.
  16. 제14항에 있어서, 제12도에 나타난 서열을 갖는 핵산.
  17. 제14항 내지 제16항중 어느 한 항에 따른 핵산을 함유하는 벡터.
  18. 제14항 내지 제16항중 어느 한 항에 따른 핵산 또는 제17항에 따른 벡터를 포함하는 숙주 세포.
  19. 제18항에 있어서, BHK, CHO, COS, HeLc, 곤충, 담배식물, 효모 또는 이. 콜라이인 숙주 세포.
  20. 제14항 내지 제16항중 어느 한 항에 따른 DNA 도는 제17항에 따른 벡터를 포함하는, 사람을 제외한, 유전자전이 포유동물.
  21. (a)제14항 내지 제16항중 어느 한 항에 따른 핵산 또는 제17항에 따른 벡터를 숙주 세포에 도입시키고, (b)숙주세포를 배양한후, (c)화합물을 분리시킴을 특징으로 하여, 제1항 내지 제8항에 따른 화합물을 제조하는 방법.
  22. (a)제18항 또는 제19항에 따른 숙주 세포를 배양하고, (b)화합물을 분리시킴을 특징으로 하여, 제1항 내지 제8항에 따른 화합물을 제조하는 방법.
  23. 약제 또는 진단 보조제를 제조하기 위한 제1항 내지 제13항중 어느 한 항에 따른 화합물의 용도.
  24. 암 치료용 약제를 제조하기 위한 제1항 내지 제13항중 어느 한 항에 따른 화합물의 용도.
  25. 제1항 내지 제13항중 어느 한 항에 따른 화합물을 포함하는 약제.
  26. 제1항 내지 제13항중 어느 한 항에 따른 화합물을 포함하는 진단보조제.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019930020298A 1992-10-02 1993-10-02 프로드럭활성화를위한융합단백질 KR100321012B1 (ko)

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DE4233152A DE4233152A1 (de) 1992-10-02 1992-10-02 Antikörper-Enzym-Konjugate zur Prodrug-Aktivierung
DEP4233182.8 1992-10-02
DEP4233152.8 1992-10-02

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ATE192193T1 (de) 2000-05-15
ZA937299B (en) 1994-04-25
NO313884B1 (no) 2002-12-16
JP3776137B2 (ja) 2006-05-17
AU4879193A (en) 1994-04-14
DE59310018D1 (de) 2000-05-31
CA2107513C (en) 2009-12-01
GR3033417T3 (en) 2000-09-29
EP0590530B1 (de) 2000-04-26
US20060292139A1 (en) 2006-12-28
AU672431B2 (en) 1996-10-03
PT590530E (pt) 2000-08-31
EP0590530A2 (de) 1994-04-06
UY23660A1 (es) 1993-10-13
DK0590530T3 (da) 2000-08-21
NO933520D0 (no) 1993-10-01
JPH06228195A (ja) 1994-08-16
US7273727B2 (en) 2007-09-25
NO933520L (no) 1994-04-05
US7060495B2 (en) 2006-06-13
NZ248818A (en) 1995-12-21
ES2147189T3 (es) 2000-09-01
US20020068329A1 (en) 2002-06-06
KR100321012B1 (ko) 2002-06-20
IL107154A (en) 2004-07-25
EP0590530A3 (en) 1997-03-26
CA2107513A1 (en) 1994-04-03

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